Hemoglobins under oxidative stress aggregate to give Heinz bodies that become attached to the cell membrane. Membrane distortion and oxidative membrane damage result in lysis of the erythrocyte. We have found that the reaction of hemoglobin with arylhydrazines gives a complex with the aryl group directly bound to the prosthetic heme iron atom and, under certain conditions, results in covalent crosslinking of the proteins. The present project is intended to (a) elucidate the structure and chemistry of the iron-aryl complexes, (b) determine if the complexes can be transferred to membranes, (c) determine if Heinz body formation can be monitored in intact erythrocytes by NMR, (d) explore the role of tyrosines proximal to the heme prosthetic groups in crosslinking, (d) investigate the mechanism and generality of direct lipid oxidation by hemoglobin, and (e) characterize sulfhemoglobin. The proposed work should provide important information not only on hemoprotein function and hemolytic mechanisms but should provide basic data relevant to the question of how damaged proteins are recognized for accelerated degradation.